1-201648790-G-T

Variant names:

• chr1-201648790-G-T
• rs1337229622
• NM_001389617.1:c.983G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001389617.1(NAV1):​c.983G>T​(p.Gly328Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000147 in 1,361,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G328A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: NAV1 NM_001389617.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146

Genes affected

NAV1 (HGNC:15989): (neuron navigator 1) This gene belongs to the neuron navigator family and is expressed predominantly in the nervous system. The encoded protein contains coiled-coil domains and a conserved AAA domain characteristic for ATPases associated with a variety of cellular activities. This gene is similar to unc-53, a Caenorhabditis elegans gene involved in axon guidance. The exact function of this gene is not known, but it is thought to play a role in in neuronal development and regeneration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2009]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16258189).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAV1	NM_001389617.1	c.983G>T	p.Gly328Val	missense_variant	Exon 5 of 34	ENST00000685211.1	NP_001376546.1
NAV1	NM_001389616.1	c.983G>T	p.Gly328Val	missense_variant	Exon 4 of 32		NP_001376545.1
NAV1	NM_001389615.1	c.983G>T	p.Gly328Val	missense_variant	Exon 5 of 31		NP_001376544.1
NAV1	NM_020443.5	c.122G>T	p.Gly41Val	missense_variant	Exon 1 of 30		NP_065176.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAV1	ENST00000685211.1	c.983G>T	p.Gly328Val	missense_variant	Exon 5 of 34		NM_001389617.1	ENSP00000510803.1
NAV1	ENST00000367296.8	c.122G>T	p.Gly41Val	missense_variant	Exon 1 of 30	5		ENSP00000356265.4
NAV1	ENST00000367302.5	c.161G>T	p.Gly54Val	missense_variant	Exon 3 of 30	5		ENSP00000356271.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000147 AC: 2 AN: 1361040 Hom.: 0 Cov.: 53 AF XY: 0.00000149 AC XY: 1 AN XY: 670066

Gnomad4 AFR exome AF: 0.0000329

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.37e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.019	.;T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.47
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Benign	0.78	T;T
M_CAP	Pathogenic	0.59	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.34	.;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.34	N;N
REVEL	Benign	0.053
Sift	Uncertain	0.0050	D;D
Sift4G	Benign	0.14	T;T
Vest4		0.21
MutPred		0.23		.;Gain of sheet (P = 0.0166);
MVP		0.082
MPC		1.2
ClinPred		0.39	T
GERP RS		-0.11
Varity_R		0.13
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1337229622; hg19: chr1-201617918;